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Rapid Publications

Cloning and Functional Expression of the Human Islet GLP-1 Receptor: Demonstration That Exendin-4 Is an Agonist and Exendin-(9–39) an Antagonist of the Receptor

  1. Bernard Thorens,
  2. Andrée Porret,
  3. Léo Bühler,
  4. Shao-Ping Deng,
  5. Philippe Morel and
  6. Christian Widmann
  1. Department of Pharmacology and Toxicology, University of Lausanne Lausanne Transplantation Unit, Department of Surgery, Geneva University Hospital Geneva, Switzerland
  1. Address correspondence and reprint requests to Dr. Bernard Thorens, Institute of Pharmacology and Toxicology, 27 Bugnon, 1005 Lausanne, Switzerland.
Diabetes 1993 Nov; 42(11): 1678-1682. https://doi.org/10.2337/diab.42.11.1678
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Abstract

A complementary DNA for a glucagon-like peptide-1 receptor was isolated from a human pancreatics islet cDNA library. The isolated clone encoded a protein with 90% identity to the rat receptor. In stably transfected fibroblasts, the receptor bound [125I]GLP-1 with high affinity (Kd = 0.5 nM) and was coupled to adenylate cyclase as detected by a GLP-1-dependent increase in cAMP production (EC50 = 93 pM). Two peptides from the venom of the lizard Heloderma suspectum, exendin-4 and exendin-(9–39), displayed similar ligand binding affinities to the human GLP-1 receptor. Whereas exendin-4 acted as an agonist of the receptor, inducing cAMP formation, exendin-(9–39) was an antagonist of the receptor, inhibiting GLP-1–induced cAMP production. Because GLP-1 has been proposed as a potential agent for treatment of NIDDM, our present data will contribute to the characterization of the receptor binding site and the development of new agonists of this receptor.

  • Received July 1, 1993.
  • Revision received August 5, 1993.
  • Accepted August 5, 1993.
  • Copyright © 1993 by the American Diabetes Association
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November 1993, 42(11)
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Cloning and Functional Expression of the Human Islet GLP-1 Receptor: Demonstration That Exendin-4 Is an Agonist and Exendin-(9–39) an Antagonist of the Receptor
Bernard Thorens, Andrée Porret, Léo Bühler, Shao-Ping Deng, Philippe Morel, Christian Widmann
Diabetes Nov 1993, 42 (11) 1678-1682; DOI: 10.2337/diab.42.11.1678

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Cloning and Functional Expression of the Human Islet GLP-1 Receptor: Demonstration That Exendin-4 Is an Agonist and Exendin-(9–39) an Antagonist of the Receptor
Bernard Thorens, Andrée Porret, Léo Bühler, Shao-Ping Deng, Philippe Morel, Christian Widmann
Diabetes Nov 1993, 42 (11) 1678-1682; DOI: 10.2337/diab.42.11.1678
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